December 21, 2020 – The European Haemophilia Consortium (EHC) has learned that uniQure announced that its haemophilia B gene therapy programme, including the pivotal, phase III HOPE-B study, has been placed on hold by the US Food and Drug Administration (FDA). The clinical hold was initiated following the submission of a safety report in mid-December relating to the possibility of a serious adverse event associated with a preliminary diagnosis of hepatocellular carcinoma (HCC), a form of liver cancer, in one patient in the HOPE-B trial that was treated with etranacogene dezaparvovec (AMT-061) in October 2019.
The male patient has multiple risk factors associated with the development of liver cancer including a history of hepatitis C (treated prior to enrollment), exposure to hepatitis B virus, evidence of non-alcoholic fatty liver disease and has advanced age. Chronic infections with hepatitis B and C have been associated with approximately 80% of HCC cases[1]. The liver lesion was detected during a routine abdominal ultrasound conducted as part of the required study assessments in patients at one-year post-dosing. A full surgical resection of the lesion is scheduled this week that will allow for confirmation of the diagnosis. uniQure has started a plan for comparison of the integration of the gene therapy in the lesion and to healthy liver tissue to determine if there is an association with the gene therapy.
No other cases of HCC have been reported in uniQure clinical trials conducted in more than 100 patients in haemophilia B and other indications, with some patients dosed more than 10 years ago, the company has stated.
The company noted that the patient dosing for the HOPE-B phase III was completed and that there was no plan to enrol any additional patient. uniQure is working closely with the FDA and their advisors to conduct a thorough investigation into the cause of this event, which they expect to complete in early 2021. All patients enrolled in the HOPE-B trial will continue to be monitored by their care teams as the company gathers additional information as rapidly as possible. The company does not anticipate any impact on its regulatory submission timeline for the haemophilia B programme as a result of this clinical hold.
The full press release is available here.
[1] El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology. 2012 May;142(6):1264-1273.e1. doi: 10.1053/j.gastro.2011.12.061. PMID: 22537432; PMCID: PMC3338949.
Jim is aged 66 and has Haemophilia A with a high titer inhibitor which he developed at age 14.
Maria Elisa Mancuso (MD, PhD) is a Haematologist and works as a Senior Haematology Consultant at the Center for Thrombosis and Haemorrhagic Diseases of IRCCS Humanitas Research Hospital in Rozzano, Milan, Italy. She is Adjunct Clinical Professor at Humanitas University. She obtained a post-degree in Clinical and Experimental Haematology and a PhD in Clinical Methodology. She is involved in clinical research and has published several original articles in peer-reviewed journals a The Lancet, Blood, Journal of Thrombosis and Haemostasis, Haematologica, Thrombosis and Haemostasis, British Journal of Haematology and Haemophilia. She is reviewer for several peer-reviewed journals and member of the Editorial Board of JTH. She is a member of several scientific societies (ISTH, WFH, ASH, EAHAD, SISET, AICE) and was a medical member of the Inhibitor Working Group of the European Hemophilia Consortium. She is co-chair of the ADVANCE Study Group. She has acted also as co-chair of the Scientific and Standardization Subcommittee of ISTH on FVIII, FIX and rare bleeding disorders. She has been involved as principal and co-investigator in several clinical trials, and she takes care of both children and adults with hemophilia and other congenital bleeding disorders with a specific scientific interest in novel therapies, prophylaxis, inhibitors, and chronic hepatitis C.
As a patient with factor II deficiency, the diagnostic and treatment of rare bleeding disorders is a matter dear to my heart. My motivation to participate in the work of the ERIN committee is to improve both diagnostic and treatment for patients with rare bleeding disorders across Europe.
Economist and financial expert by profession, executive coach and trainer by passion and haemophilia advocate by every drop of my blood through my son (who has severe haemophilia A with inhibitors). Bringing a good decade of practical experience from the corporate insurance world, laser focus, growth mindset and resilience from my own experience, offering you anything I can just do, in hope that together we can make life more fulfilled for those impacted by bleeding disorders.
Amy Owen-Wyard is a Registered Mental Health Nurse. With experience working with children, young people, their families and adults with severe and enduring mental health conditions. Amy was also involved in a service improvement to provide a holistic care approach for those in general hospitals to support both their mental and physical health, whilst sharing her expertise and knowledge in mental health with the wider multidisciplinary team.
